Download Evaluation of upper airway patency during Cheyne–Stokes breathing in heart failure patients

Eur Respir J 2012; 40: 1523–1530
DOI: 10.1183/09031936.00060311
CopyrightßERS 2012
Evaluation of upper airway patency
during Cheyne–Stokes breathing in heart
failure patients
Vincent Jobin*,#, Jordi Rigau",+, Josée Beauregard*, Ramon Farre",
Josep Monserrat1, T. Douglas Bradleye and R. John Kimoff*
ABSTRACT: Little is known about the changes in upper airway calibre in Cheyne–Stokes
respiration (CSR) during sleep in patients with congestive heart failure. This study aimed to test
the hypothesis that upper airway closure occurs during central CSR events, by assessing upper
airway calibre during sleep using the forced oscillation technique (FOT).
Nine males with compensated heart failure (left ventricular ejection fraction mean¡SEM
27.9¡5.1%) and predominant central CSR (apnoea/hypopnoea index 43.9¡4.2 events?h-1) were
studied during overnight polysomnography, which included pneumotachography, inductance
plethysmography or oesophageal pressure and FOT-derived impedance signal (|Z|).
Baseline |Z| values during stable breathing in stage 2 sleep were 11.0¡1.3 cmH2O?s?L-1. Mean
|Z| increased to 31.9¡6.7 cmH2O?s?L-1 during obstructive apnoeas (7% of events, n546).
Increases in |Z| consistent with upper airway narrowing (more than two-fold baseline) were
common during central apnoeas (50¡12% of events) occurring in the middle or end of apnoeas and
occurred during some central hypopnoeas (16¡10% of events), typically in the expiratory phase.
These findings indicate that in heart failure patients, reductions in upper airway calibre are
common during CSR apnoeas, and may also occur during central hypopnoeas.
KEYWORDS: Central sleep apnoea, Cheyne–Stokes breathing, forced oscillation, upper airway
heyne–Stokes respiration (CSR) during
sleep is prevalent among patients with
congestive heart failure (CHF) [1] and is
associated with increased mortality [2, 3] The
pathophysiology of CSR remains incompletely
understood. A key factor triggering central apnoeas
is a reduction in carbon dioxide tension below the
apnoea threshold [1], which is related to sleep–
wake instability, altered ventilatory and cerebrovascular carbon dioxide chemosensitivity, prolonged
circulation time and stimulation from pulmonary
irritant receptors [1, 4–6]. However, the observation that there may be a shift between obstructive
and central apnoeas in CSR-CHF [7, 8], that CSR
can be affected by posture, [9, 10] and that it may
be suppressed by continuous positive airway
pressure (CPAP) in some patients [11] suggests
that upper airway instability may also play a role
in this disorder. Dynamic changes in upper airway
calibre might, therefore, be a further factor
contributing to ventilatory instability in CSR-CHF.
C
However, upper airway patency during central
apnoeas and hypopnoeas has not been systematically investigated in patients with CHF.
The forced oscillation technique (FOT) is a noninvasive method for instantaneous measurement
of respiratory system mechanics which has been
shown to be reliable in assessing upper airway
calibre during sleep in patients with obstructive
sleep apnoea (OSA) [16–18]. FOT systems have
been developed which measure impedance (|Z|
cmH2O?s?L-1) of the respiratory system during
sleep in a continuous fashion without disturbing
sleep architecture or altering upper airway muscle
tone [19]. FOT has been shown to be a sensitive
indicator of dynamic changes in upper airway
calibre during obstructive events [17] and can be
used to detect respiratory events and guide CPAP
titration [16, 20, 21].
Upper airway closure has previously been reported
to occur in some forms of both spontaneous and
experimentally induced central apnoea [7, 12–15].
In the present study, we hypothesised that in
CHF patients with CSR, upper airway closure
would occur during central apnoeas and hypopnoeas. The objective of the study was to evaluate
changes in upper airway calibre during CSR
using FOT.
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VOLUME 40 NUMBER 6
AFFILIATIONS
*Respiratory Division, MeakinsChristie Laboratories, McGill
University,
#
Dept de Pneumologie, Centre
Hospitalier de l’Université de
Montreal, Montreal, QC, and
e
Dept of Medicine, University of
Toronto, Toronto, ON, Canada.
"
Lab. Biofisica i Bioenginyeria,
Facultat Medicina, Universitat de
Barcelona-IDIBAPS and CIBERES de
Enfermedades Respiratorias,
+
RDI Dept, SIBEL S.A., and
1
Servei de Pneumologia, Institut del
Tòrax and CIBERES de Enfermedades
Respiratorias, Barcelona, Spain.
CORRESPONDENCE
R.J. Kimoff
Respiratory Division, Rm L4.08
McGill University Health Centre
687 Pine Ave W.
H3A 1A1
Montreal
QC
Canada
E-mail: [email protected]
Received:
April 07 2011
Accepted after revision:
April 11 2012
First published online:
May 17 2012
European Respiratory Journal
Print ISSN 0903-1936
Online ISSN 1399-3003
c
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HEART AND LUNG INTERACTION
V. JOBIN ET AL.
METHODS
Subjects
Nine patients with stable chronic CHF being screened for the
CANPAP study [11] were recruited from the Sleep Disorders
and Cardiac Function Clinics of the McGill University Health
Centre (Montreal, QC, Canada). The Research Ethics Board
approved the study protocol and subjects provided written
informed consent.
Eligibility requirements have been described in full elsewhere
[22]. Briefly, subjects were adults with stable CHF due to
ischaemic, idiopathic or hypertensive cardiomyopathy with left
ventricular ejection fraction ,40% (by radionuclide angiography) and o15 apnoeas and hypopnoeas per hour of sleep
(apnoea/hypopnoea index (AHI)), of which .50% were central
at screening polysomnography (PSG). We recruited eligible
subjects who either declined participation in the main study or
were studied before randomisation within CANPAP.
Experimental protocol
After initial screening PSG to determine eligibility, each subject
underwent a subsequent overnight (n58) or daytime (n51)
conventional polysomnogram with the addition of oesophageal pressure (Poes) monitoring when tolerated by the subject,
and a sealed face mask connected to the FOT circuit for
measurement of respiratory system impedance (|Z|).
Each polysomnogram was initially scored in a standard manner
(sleep and respiratory events) [11] by a trained polysomnographic technologist. Following this, FOT-derived impedance
values during respiratory events in non-rapid eye movement
(REM) sleep were assessed as described below.
Measurements
Polysomnography
The following signals were included. 1) Electroencephalogram
(C4A1, C3A2), chin electromyogram, electrocardiogram and
electrooculogram which were recorded and scored for sleep
stages and arousals according to standard criteria [23, 24].
2) Nocturnal arterial oxygen saturation measured by pulse
oximetry (Ohmeda Biox 3700; Roxon Inc., Montreal, ON,
Canada). 3) Rib cage and abdominal movements by inductance
plethysmography (Respitrace; Ambulatory Monitoring Inc.,
Ardsely NY, USA). 4) Poes measured using a balloon-tipped
catheter attached to a differential pressure transducer (Validyne,
Northridge, CA, USA) and airflow and oscillatory impedance
using the FOT device as described below. These variables were
simultaneously recorded using a standard PSG system (Sandman,
Ottawa, ON, Canada) and a second computerised system
(CODAS; DATAQ Instruments, Akron, OH, USA) for subsequent
respiratory signal processing. At least 3 h of sleep were required
in order for PSG data to be included in the final analysis.
Oscillatory impedance measured using the FOT
FOT was applied as previously described [17, 18, 25]. A fullface mask was connected to a mesh wire-based pneumotachograph (resistance50.522 L?s-1) connected to a T-piece. One arm
of the T-piece was connected (Tb1) to a chamber with a
loudspeaker (8BR40; Beyma, Valencia, Spain) and the other
arm to a tube (Tb2) acting as a pneumatic low-pass filter. A
continuous bias flow (0.4 L?s-1) through all the tubing was
applied to the system in order to avoid rebreathing. A small
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VOLUME 40 NUMBER 6
amplitude (1 cmH2O peak-to-peak) pressure oscillation of 5 Hz
was generated with the loudspeaker and applied on the mask
while the patient breathed spontaneously. Mask pressure and
flow signals were measured with differential pressure transducers (range ¡9 and 2 cmH2O, respectively; Validyne). The
frequency responses at 5 Hz of the flow and pressure transducers were matched within 1% in gain and 1u in phase. Special
attention was paid to avoid leaks by carefully fitting the full-face
mask. The raw flow and pressure signals were analogically lowpass filtered (8-pole Butterworth, 32 Hz) and introduced into a
microprocessor-based system for digital on-line computation of
|Z| [26]. This signal was recorded on the polygraph, as well as
in the CODAS acquisition system as an additional channel.
Data analysis
Scoring of respiratory events
Scoring criteria for respiratory events were identical to those
used in the CANPAP study [11], although with substitution in
the present study of the pneumotachograph airflow signal for
nasal pressure, and the availability of additional information
concerning respiratory effort in subjects with Poes catheters in
place. CSR was defined as repetitive cycles of apnoeas and/or
hypopnoeas, alternating with hyperpnoeas which had a
crescendo/decrescendo pattern of tidal volume, occurring at
a rate of .15 events?h-1 of sleep. Central apnoeas were defined
as the absence of tidal volume for o10 s without thoracoabdominal motion and central hypopnoeas as a reduction of
o50% in tidal volume from baseline for o10 s with flow
paralleling Poes and/or thoraco-abdominal displacement, and
without clear inspiratory airflow limitation on the pneumotachograph signal. Apnoeas and hypopnoeas were classified as
obstructive if there was out-of-phase motion of the rib cage and
abdomen, incremental respiratory effort disproportionate to
flow on Poes tracing, or clear inspiratory airflow limitation on
the pneumotachograph signal.
Measurements of impedance values |Z| during apnoeas and
hypopnoeas
We analysed impedance in one out of five CSR events in each
patient, with the first event randomly selected then every fifth
consecutive event analysed. For obstructive events, due to the
small number, all events observed were analysed.
Impedance was measured during the apnoeic or hypopnoeic
period of the CSR cycle. For apnoeas, measurements of
impedance were performed by computing the mean |Z| value
of a 2-s window at the beginning, middle and end of the apnoea.
For hypopnoeas, to determine the beginning and end of the
measurement period, we defined a threshold flow as 50% of the
mean of the 10 peak values of inspiratory flow during stable
respiration (without CSR or OSA) in supine stage 2 sleep. A
hypopnoea began with the first cycle that included a peak
inspiratory flow below the threshold flow and it ended with the
last cycle that contained a peak inspiratory flow below the
threshold flow. To measure |Z| values during hypopnoea, first,
the mean mid-inspiratory |Z| value (window50.4 s at the
middle of inspiration) for 10 consecutive breathing cycles of
spontaneous normal breathing was averaged in order to obtain
a normalised inspiratory value (stage 2 supine or awake if not
available during sleep). The same analysis was performed with
the corresponding expiratory cycle phases in order to obtain a
EUROPEAN RESPIRATORY JOURNAL
V. JOBIN ET AL.
HEART AND LUNG INTERACTION
normalised mid-expiratory value. Then, inspiratory degree of
occlusion was calculated by averaging the mid-inspiratory
value (window50.4 s) for each respiratory cycle during the
event and expiratory degree of occlusion was calculated by
averaging the mid-expiratory value (window50.4 s) for each
respiratory cycle during the event.
Previous studies in patients with OSA have indicated that
major upper airway narrowing or collapse can be reliably
identified when the impedance value increases to levels more
than twice baseline values during tidal breathing [16, 27].
Therefore, for the various categories of respiratory events we
determined the proportion of events for which |Z| exceeded
this value.
Statistical analysis
FOT-derived impedance |Z| values were expressed as absolute
values or as percentage of baseline |Z| value during stable
breathing. |Z| values during stable breathing, central and
obstructive apnoeas and hypopnoeas were normally distributed
and mean values were compared using unpaired t-tests.
Correlations between anthropometric or clinical measures and
|Z| values were assessed using Pearson’s product-moment
coefficient. Data are expressed as mean¡SEM, unless otherwise specified. A threshold of p,0.05 was used for statistical
significance.
RESULTS
Subject characteristics are presented in table 1. On the original
diagnostic polysomnograms, the apnoea index was 30.5¡3.6
events?h-1, total sleep time was 5.2¡0.8 h and 66.3¡3.6% of
events were central. CHF aetiology was ischaemic in six subjects
and idiopathic in three. New York Heart Association class was II
in four subjects and III in five subjects. Placement of an
oesophageal catheter was attempted in all subjects but was
unsuccessful due to discomfort in four. Subject characteristics
TABLE 1
Subject
were not significantly different between those with versus those
without oesophageal catheters.
Representative tracings of typical respiratory events are shown
in figures 1–3. Figure 1a illustrates the impedance signal during
central apnoeas during the CSR cycle in which the impedance
value remained low throughout. In contrast, figure 1b shows
central apnoeas during which the impedance signal increased
substantially during the course of the events, followed by a
rapid fall to baseline as soon as respiratory effort was initiated.
Figure 2 illustrates central hypopnoeas as evidenced by the
changes in airflow paralleling changes in respiratory effort.
Impedance values during hypopnoeas were often increased
above baseline values during stable breathing, most often during
the hypopnoeic phase of the CSR cycle (fig. 2a) but in some cases
across the CSR cycle (fig. 2b). |Z| values tended to be higher
during expiration and fell during inspiration. This pattern was
observed in five of the eight subjects with central hypopnoeas.
Overall, however, mean |Z| values during the expiratory phase
were not significantly higher than during the inspiratory phase
(15.7¡0.8 versus 14.9¡1.1 cmH2O?s?L-1; p50.81).
We observed a small number of obstructive events in this
patient group. One example is shown in figure 3 with the
typical CSR pattern of effort during absent airflow, followed by
a sudden resumption of airflow with airway re-opening. The
impedance signal increases progressively during the obstructive event with, initially, impedance increasing during inspiratory effort and decreasing during the expiratory phase,
followed by consistently high values indicative of persistent
airway closure, followed by a rapid fall in impedance at airway
re-opening.
A total of 647 events were analysed, the majority of which were
central (table 1). As noted previously, for central events, every
fifth event was analysed, while all obstructive events observed
were analysed. All nine subjects demonstrated central apnoeas
Subject characteristics and proportion of respiratory events with increased forced oscillation technique-derived
impedance signal (|Z|)
Age yrs
BMI kg?m-2
LVEF %
AHI# events per h
Central apnoeas"
Events n
|Z| .26
Central hypopnoeas"
Events n
proportion1
|Z| .26
OAH+
Events n
proportion1
1
47
24.3
5
40.8
29
0.34
14
0.00
6
2
68
25.7
20
57.2
110
0.72
97
0.40
18
3
76
32.4
39
62.9
34
0.62
45
0.38
4
84
31.2
33
48.9
60
0.20
29
0.07
5
59
48.7
29
24.2
37
1.00
6
70
24.3
38
28.0
16
0.00
2
0.00
7
60
23.0
23
44.8
10
1.00
2
0.00
22
8
70
31.0
40
58.0
12
0.08
14
0.14
13
9
63
24.5
23
50.0
48
0.56
16
0.31
66.3¡3.4
29.5¡2.7
27.9¡3.8
46.1¡4.4
Mean¡SE
0.50¡0.12
0.16¡0.10
BMI: body mass index; LVEF: left ventricular ejection fraction; AHI: apnoea/hypopnoea index; OAH: obstructive apnoeas and hypopnoeas. #: from original diagnostic
polysomnogram; ": from study night, every fifth event analysed; +: from study night, all events analysed; 1: proportion of events with |Z| greater than two-fold baseline
values (see Methods).
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VOLUME 40 NUMBER 6
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c
a)
1
V' L·s-1
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0
V. JOBIN ET AL.
b)
|Z| cmH2O·s·L-1 Poes cmH2O
-1
5
0
-15
20
0
FIGURE 1.
Examples of central Cheyne–Stokes respiration apnoeas with absence of airflow and respiratory effort from the same patient in which a) the forced oscillation
technique-derived impedance signal (|Z|) remains low throughout the event, and b) |Z| increases during the course of the event. V9: gas flow (a positive value indicates
inspiration); Poes: oesophageal pressure.
(40¡10 events analysed per subject), eight out of nine
demonstrated central hypopnoeas (27¡11 events analysed
per subject), while four subjects demonstrated obstructive
events (18¡3 analysed per subject).
The mean baseline FOT-derived impedance value during stable
breathing in non-REM sleep was 11.0¡1.3 cm H2O?s?L-1. For the
different categories of respiratory events, mean |Z| values for
central hypopnoeas (34% of total events analysed), central
apnoeas (55% of events), obstructive hypopnoeas (4% of events)
and obstructive apnoeas (7% of events) were 15.3¡1.7 cmH2O?
s?L-1, 27.3¡5.9 cmH2O?s?L-1, 30.6¡11.5 cmH2O?s?L-1 and 31.9¡
6.7 cmH2O?s?L-1, respectively. All of these values were significantly greater than baseline (p,0.005).
Figure 4 shows mean values for |Z| during the first, middle and
latter third of apnoeas for central versus obstructive apnoeas.
While values during obstructive events tended to be higher,
there were substantial increases in mean |Z| during central
events indicating prominent degrees of upper airway closure.
Figure 5 illustrates the proportion of respiratory events during
which upper airway closure occurred as defined by a criterion
of |Z| reaching twice the baseline value during stable breathing. Given the small number of obstructive events, apnoeas and
hypopnoeas were pooled for this analysis. For central hypopnoeas, five subjects demonstrated varying degrees of upper
airway closure. For central apnoeas, the frequency of upper
airway closure during events also varied between subjects, with
upper airway closure occurring rarely or not at all in some
subjects but in a majority of events in others. The upper airway
was more likely to be occluded during central apnoeas than
hypopnoeas as shown by the significantly higher proportion
of events with |Z| values exceeding the baseline values for
central apnoeas compared with hypopnoeas (0.50¡0.12 versus
0.16¡0.1, p50.03).
There were no systematic differences in subject characteristics
including age, body mass index, left ventricular ejection
fraction, AHI or other measures of apnoea severity between
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VOLUME 40 NUMBER 6
subjects with frequent versus rare or absent upper airway
closure during central events (table 1). Airway closure during
central events was not consistently related to the occurrence of
obstructive events in the same subjects. There was a trend to a
positive correlation between body mass index and baseline
pre-event |Z| value (r50.64, p50.06). No significant correlations were identified between anthropometric measures and
the proportions shown in figure 5. For the four subjects who
demonstrated occasional obstructive events, |Z| values during central apnoeas were high in two and low in the other two.
DISCUSSION
In this study, we applied the FOT to assess upper airway
patency during predominantly central sleep apnoeas and
hypopnoeas in subjects with compensated chronic CHF. We
found that airway closure occurred, to a variable extent, during
central apnoeas, with some patients frequently demonstrating
airway closure, and others rarely demonstrating evidence of
upper airway collapse. Upper airway narrowing was less
common during CSR hypopnoeas than apnoeas, and during
hypopnoeas, upper airway impedance tended to be higher
during expiration than inspiration.
The FOT-derived impedance |Z| signal has previously been used
to identify upper airway obstruction during sleep in OSA [17].
Upper airway closure is a dynamic process in OSA associated
with an instantaneous large increase in respiratory resistance,
which cannot be accounted for by other changes within the
respiratory system. One limitation of our study is that we did not
directly visualise the upper airway. However, invasive techniques
such as video-endoscopy would probably be poorly tolerated in
CHF patients whose sleep quality is generally poor. The values of
the impedance signal observed during obstructive events in the
present study were comparable with those previously described
in severe OSA (|Z|536¡8 cmH2O?s?L-1) [12] supporting the
conclusion that high impedance values observed during central
events were indeed indicative of substantial upper airway
narrowing.
EUROPEAN RESPIRATORY JOURNAL
1
b)
1
0
0
-1
5
5
Poes cmH2O
-1
|Z| cmH2O·s·L-1
-15
30
0
1
0
-15
30
0
d) 0.6
V' L·s-1
c)
V' L·s-1
|Z| cmH2O·s·L-1
Poes cmH2O
a)
V' L·s-1
HEART AND LUNG INTERACTION
V' L·s-1
V. JOBIN ET AL.
0
-0.6
30
20
|Z| cmH2O·s·L-1
|Z| cmH2O·s·L-1
-1
0
FIGURE 2.
0
Representative tracings of central Cheyne–Stokes respiration (CSR) hypopnoeas with the variation in airflow paralleling respiratory effort. a) The forced
oscillation technique-derived impedance signal (|Z|) increases in expiration during the hypopnoeic phase of the CSR cycle. b) Magnified view of the segment indicated by
the arrow in (a) illustrating the increase in |Z| during the expiratory phase of the respiratory cycle. c) Tracings from another subject in whom expiratory |Z| values remain
elevated across the CSR cycle with discrete reductions in |Z| during inspiration. d) Magnified view of the segment indicated by the arrow in (c). V9: gas flow; Poes:
oesophageal pressure.
Another potential limitation of the study was the inability of
four of the nine subjects to tolerate an oesophageal catheter,
which can be a useful signal in distinguishing central from
obstructive hypopnoeas. Only central apnoeas were observed
in one of the four subjects without Poes, and in the other three
subjects the number of central apnoeas sampled/analysed
outnumbered central hypopnoeas two-fold. Nonetheless, in
the latter subjects we were confident of the central nature of the
events so designated, based on the pneumotachography and
inductance plethysmography signals, as well as the characteristic pattern of |Z| changes during these events (fig. 2 versus
fig. 3). Another potential limitation of the study was the
relatively small number of subjects which may have restricted
our ability to identify anthropometric and other clinical factors
in contributing to upper airway collapse.
The findings of the present study are in accordance with previous
studies providing direct evidence of upper airway collapse
during spontaneous or induced central apnoeas/hypopnoeas
using acoustic or video-endoscopic techniques [13, 15]. More
recently, VANDERVEKEN et al. [12] applied FOT in eight patients
with predominantly OSA and demonstrated variable increases in
|Z| during a small number of central apnoeas. However, to our
knowledge, ours is the first study to assess upper airway calibre
with FOT in a group consisting of exclusively stable CHF patients
with predominantly central events.
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VOLUME 40 NUMBER 6
FOT alone does not permit determination of the specific site of
upper airway obstruction, or whether airway closure is passive
or active. Reductions in pharyngeal cross-sectional area level
have been observed by video-endoscopy during spontaneous
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c
1
0
V. JOBIN ET AL.
b)
Proportion of events with upper airway closure
a)
V' L·s-1
HEART AND LUNG INTERACTION
5
-15
|Z| cmH2O·s·L-1
Poes cmH2O
-1
60
1.0
*
0.8
0.6
#
0.4
0.2
0.0
Central
hypopnoeas
Central
apnoeas
Obstructive
events
0
FIGURE 5.
FIGURE 3.
Representative tracings of an obstructive hypopnoea with a
Cheyne–Stokes respiration pattern of respiratory effort. a) The forced oscillation
technique-derived impedance signal (|Z|) increases in concert with increasing
respiratory effort, followed by an abrupt fall signalling airway re-opening at the end
Proportion of respiratory events with forced oscillation technique-
derived impedance signal (|Z|) increases consistent with upper airway closure (|Z|
.26 baseline value) by event type. Symbols indicate individual patient values.
Group mean¡SE values are indicated by error bars. *: p,0.05 versus central events
(hypopnoeas or apnoeas). #: p,0.05 versus central hypopnoeas.
of the obstructive event. b) Magnified view of the segment indicated by the arrow in
(a). The marked increases in impedance are occurring during the inspiratory phase
consistent with dynamic inspiratory airway collapse.
idiopathic central apnoeas [13, 15]. In one study [13], electromyogram recordings demonstrated that pharyngeal constrictors
were inactive, suggesting passive airway closure. In addition,
SANKRI-TARBICHI et al. [14] and BADR et al. [15] observed
diminished pharyngeal cross-sectional area on video-endoscopy associated with increased upper airway resistance during
induced central hypocapnic hypopnoea. Of note, retropalatal
narrowing under these low drive/hypotonic conditions
occurred predominantly during the expiratory phase [14]. In
60
Central apnoeas
Obstructive apnoeas
|Z| cmH2O·s·-1
50
40
30
20
10
First
Middle
Latter
Apnoea segment
FIGURE 4.
Group mean¡SE values for the forced oscillation technique-
derived impedance signal (|Z|) during the first, middle and latter third of Cheyne–
Stokes respiration central apnoeas compared with obstructive apnoeas.
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VOLUME 40 NUMBER 6
our study, the development of upper airway closure during the
course of central apnoeas, with immediate airway re-opening
associated with the onset of inspiratory effort and airflow
(figs 1b and 4) could be consistent with passive pharyngeal
collapse during the apnoea phase followed by active re-opening
of the airway as inspiratory drive resumes.
During CSR hypopnoeas, some subjects demonstrated substantial increases in |Z| values compared with stable breathing periods at similar lung volumes as judged from respiratory
inductance plethysmography signals, consistent with upper
airway narrowing. This was most prominent during the
hypopnoeic phase of the cycle (fig. 2), and impedance tended
to be higher in expiration and fall during inspiration. Lung
volume changes could potentially have contributed to the
inspiratory decrease in |Z|, and the increased expiratory
impedance during the hypopnoeic phase could reflect dynamic
narrowing of intrathoracic large airways although this seems
unlikely in the context of reduced drive. It seems more likely
that the expiratory increase in |Z| is reflective of passive
upper airway narrowing during the period of reduced drive.
The inspiratory fall could also represent active inspiratory
airway opening. Our observations during both CSR apnoeas
and hypopnoeas are, therefore, consistent with passive upper
airway narrowing due to withdrawal of inspiratory drive to
the pharyngeal dilators.
However, upper airway calibre could also be actively
diminished at the laryngeal level since it has been shown that
vocal cord adductors are activated and abductors are suppressed during induced hypocapnia in animals [28], as well as
in humans [29].
While this seems somewhat less likely in the context of CSR,
the mechanisms and site of upper airway closure in central
sleep apnoea-CSR may differ between individuals, depending
upon upper airway anatomy, carbon dioxide responsiveness
EUROPEAN RESPIRATORY JOURNAL
V. JOBIN ET AL.
and other factors [14, 15]. Ideally, innovative noninvasive
imaging techniques should be combined with electromyographic studies to further characterise upper airway narrowing
in CSR-CHF.
The observation of supine-dependence of central sleep apnoeaCSR [9, 10] and responses to fixed CPAP in some patients [11]
suggest that upper airway narrowing during CSR events may
contribute to the pathogenesis of this condition. This could be
mediated through reflex inhibitory effects of upper airway
closure, which may precipitate or prolong central apnoeas [30].
Variations in upper airway calibre could be a contributing
factor to ventilatory instability, promoting ventilatory overshoot with abrupt decreases in upper airway resistance or
dampening compensatory responses in the context of high
resistance [31]. The frequent occurrence of reduced airway
calibre during central CSR events in some subjects with central
CSR also sheds light on the previously reported overlap
between CSR and OSA [7, 8]. When airway calibre is reduced,
conceivably only small changes in airway dimensions related
to respiratory drive, tissue fluid shifts or changes in lung
volume would be required to either promote or alleviate an
inspiratory obstructive component to periodic breathing.
The findings of this study also suggest potential clinical
applications for FOT in CSR-CHF patients. For diagnostic
purposes, FOT-derived impedance during CSR hypopnoeas
could assess inspiratory upper airway obstruction. Increased
impedance could potentially be a marker for a response of CSR
to fixed CPAP [11], although this remains to be tested. In
addition, FOT-driven auto-CPAP has been used successfully in
OSA [32]. Conceivably, FOT-derived impedance could be
incorporated into servo-ventilation algorithms to adjust endexpiratory pressure levels to assure upper airway patency
during the treatment of CSR.
In conclusion, our findings support the hypothesis that in CHF
patients with CSR, upper airway closure occurs commonly
during CSR apnoeas, and may also occur during central
hypopnoeas in non-REM sleep. Further studies are needed to
identify the specific site and mechanism of occlusion and the
possible contribution of upper airway closure to the pathophysiology of CSR.
SUPPORT STATEMENT
This study was funded by l’Association Pulmonaire du Québec and by
an operating grant from the Canadian Institutes of Health Research
through its University Industry Program (UI-14909) in partnership
with Respironics Inc., ResMed Inc. and Tyco Healthcare.
STATEMENT OF INTEREST
A statement of interest for R.J. Kimoff and the study itself can be found
at www.erj.ersjournals.com/site/misc/statements.xhtml
ACKNOWLEDGEMENTS
We thank C. Barber, research co-ordinator (McGill University Health
Centre, Montreal, QC, Canada, and the sleep laboratory technical staff
at the McGill University Health Centre.
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